This invention relates to a pain-alleviating drug composition and method for alleviating pain. The drug composition includes as a first component a first analgesic which may be of the opioid type, e.g., codeine, dihydrocodeine, oxycodone, hydrocodone, meperidine, propoxyphene, pentazocine, etc., or of the nonopioid type, e.g., a coal tar analgesic such as acetaminophen or a nonsteroidal antiinflammatory drug (NSAID) such as aspirin or ibuprofen, as a second component, a sedative, e.g., of the barbiturate type such as butalbital or of the nonbarbiturate type such as diphenhydramine, dichloralphenazone, droperidol or promethazine, a skeletal muscle relaxant such as methocarbamol or carisoprodol and, where the first analgesic is of the opioid type, a second analgesic of the nonopioid type, e.g., acetaminophen, aspirin or ibuprofen, and as a third component, a nontoxic N-methyl-D-aspartate (NMDA) receptor antagonist such as dextrorphan or dextromethorphan.
A number of drug combinations for alleviating pain or treating other conditions associated with a pain component are known including the following: codeine phosphate and acetaminophen; hydrocodone bitartrate and acetaminophen; codeine phosphate and aspirin; hydrocodone bitartrate, acetaminophen, caffeine, chlorpheniramine maleate and phenylephrine hydrochloride; hydrocodone bitartrate and aspirin; dihydrocodeine bitartrate, acetaminophen and caffeine; dihydrocodeine bitartrate, aspirin and caffeine; codeine phosphate and promethazine hydrochloride; meperidine hydrochloride and promethazine hydrochloride; oxycodone hydrochloride and acetaminophen; oxycodone hydrochloride, oxycodone terephthalate and aspirin; pentazocine hydrochloride and acetaminophen; pentazocine hydrochloride and aspirin; propoxyphene napsylate and acetaminophen; propoxyphene hydrochloride and acetaminophen; propoxyphene hydrochloride, aspirin and caffeine; acetaminophen and diphenhydramine citrate; acetaminophen and diphenhydramine hydrochloride; acetaminophen, dichloralphenazone and isometheptene mucate; aspirin and butalbital; acetaminophen, butalbital and caffeine; aspirin, butalbital and caffeine; codeine phosphate, aspirin, butalbital and caffeine; aspirin and methocarbamol; aspirin and carisoprodol; codeine phosphate, aspirin and carisoprodol; and, fentanyl citrate and droperidol.
The analgesic component(s) of each of these combination drugs can cause adverse reactions. Opioid analgesics such as codeine, dihydrocodeine, oxycodone, hydrocodone, meperidine, propoxphene and pentazocine can produce tolerance and/or dependence. As for the nonopioid analgesics, acetaminophen has been known to cause fatal hepatic damage and the NSAIDs have a tendency to cause gastrointestinal side effects ranging from the relatively mild to the guite severe (ulceration of the stomach or duodenum). The risk of these adverse reactions is all the greater where their long term administration is concerned.
Dextromethorphan is the d-isomer of the codeine analog of levorphanol. Unlike the l-isomer, dextromethorphan is said to have no analgesic or addictive properties (Goodman and Gilman's, "The Pharmacological Basis of Therapeutics", 8th ed., McGraw-Hill, Inc. (1990), p. 518). The antitussive activity of dextromethorphan has led to its use in a variety of over-the-counter orally administered therapeutic compositions (tablets, syrups) for the relief of cold, influenza and/or cough conditions. Many, if not most, of these therapeutics also contain a nonopioid analgesic such as an NSAID.
U.S. Pat. No. 4,446,140 describes a method of treating mouth pain, i.e., pain or discomfort associated with the oral cavity, the teeth, gums and other mucosal surfaces of the lips, tongue and mouth resulting from such causes as toothache, denture irritations, canker sores, irritation related to inflamed gums, orthodontic tooth manipulation and appliances, oral surgery, etc., by administration of dextromethorphan alone or together with a conventional analgesic such as acetaminophen, indomethacin, ibuprofen or naproxen or a conventional anesthetic such as benzocaine or butacaine.
U.S. Pat. No. 5,321,012 discloses that administration of a nontoxic NMDA receptor antagonist such as dextrorphan or dextromethorphan prior to, with or following administration of an opioid analgesic such as morphine, codeine, and the like, inhibits the development of addiction to and/or dependence on the analgesic.
European Patent Application 0 081 823 describes a method of temporarily reducing pain and discomfort associated with dysmenorrhea by administration of dextromethorphan alone or in combination with one or more additional drugs, e.g., an analgesic such as acetaminophen, indomethacin, ibuprofen or naproxen.